In the proposed research, dicationic electrophilic chemical systems will be studied. Many potent drugs are electrophilic species that react with nucleophilic sites on proteins (i.e., enzyme inhibitors) and nucleic acids (i.e., chemotherapy alkylating agents). The proposed work is relevant to the structure-activity relationships of these types of drugs, as it will reveal the mechanisms by which electrophiles are made more reactive. Specifically, the work shall establish the scope of dicationic chemistry by determining what types of chemical structures are prone to form reactive, dicationic electrophiles. Mechanistic studies will also determine how dicationic electrophiles tend to react. Included in this phase of the work will be the study of a novel metal free, dehydrogenase enzyme system. These research goals will be accomplished by the study of appropriately designed model systems in condensed phase, acid-catalyzed reactions. Using theoretical and spectroscopic methods, the structures and energies of these electrophilic systems will also be studied. Since dicationic electrophiles often exhibit high reactivities, it is proposed that these species can be exploited in organic synthesis. Using acid-catalyzed reactions involving dicationic electrophiles, synthetic targets will include various neuropharmaceuticals (anti-depressants, anti-convulsants, and anti-spasmodics), as well as products which could be useful in the treatment of cystic fibrosis. Some the synthetic chemistry may also be capable of preparing substances useful in the treatment of drug addiction. A number of clinically important drugs are functionalized with electron-deficient aryl groups. The proposed work will demonstrate that these groups can be readily incorporated into the reaction products by exploiting the reactivity of dicationic electrophiles. These results may enable medicinal chemists to prepare more effective pharmaceuticals and lower the cost of production for these drugs.